4.7 Article

A dual-enzyme cleavable linker for antibody-drug conjugates

期刊

CHEMICAL COMMUNICATIONS
卷 57, 期 28, 页码 3457-3460

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ROYAL SOC CHEMISTRY
DOI: 10.1039/d1cc00957e

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  1. EPSRC [EP/P020291/1] Funding Source: UKRI

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A novel enzyme cleavable linker for antibody-drug conjugates, utilizing a highly hydrophilic dual-cleavable 3-O-sulfo-beta-galactose linker, shows excellent cytotoxicity and selectivity in targeted cells when used to synthesize an alpha-HER2 antibody-drug conjugate.
A novel enzyme cleavable linker for antibody-drug conjugates is reported. The 3-O-sulfo-beta-galactose linker is cleaved sequentially by two lysosomal enzymes - arylsulfatase A and beta-galactosidase - to release the payload in targeted cells. An alpha-HER2 antibody-drug conjugate synthesised using this highly hydrophilic dual-cleavable linker exhibited excellent cytotoxicity and selectivity.

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